Lancet neurology
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Multiple system atrophy (MSA) is a sporadic and rapidly progressive neurodegenerative disorder that presents with autonomic failure in combination with parkinsonism or cerebellar ataxia. Over the past 5 years, substantial progress has been achieved in understanding the pathogenesis of the disease. Important insights into the epidemiology and genetics of MSA have confirmed the key pathogenic role of alpha-synuclein. ⋯ Finally, novel therapeutic options targeting disease modification have been investigated in clinical trials. These include riluzole, recombinant human growth hormone, and minocycline. Although the trials did not find any positive effects on disease progression, they generated important trial expertise in MSA and were only possible because of the establishment of international networks.
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Prediction of susceptibility to multiple sclerosis (MS) might have important clinical applications, either as part of a diagnostic algorithm or as a means to identify high-risk individuals for prospective studies. We investigated the usefulness of an aggregate measure of risk of MS that is based on genetic susceptibility loci. We also assessed the added effect of environmental risk factors that are associated with susceptibility for MS. ⋯ The inclusion of 16 susceptibility alleles into a wGRS can modestly predict MS risk, shows consistent discriminatory ability in independent samples, and is enhanced by the inclusion of non-genetic risk factors into the algorithm. Future iterations of the wGRS might therefore make a contribution to algorithms that can predict a diagnosis of MS in a clinical or research setting.
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Randomized Controlled Trial Multicenter Study
Stroke treatment with alteplase given 3.0-4.5 h after onset of acute ischaemic stroke (ECASS III): additional outcomes and subgroup analysis of a randomised controlled trial.
In the European Cooperative Acute Stroke Study III (ECASS III), alteplase administered 3.0-4.5 h after the onset of stroke symptoms resulted in a significant benefit in the primary endpoint (modified Rankin scale [mRS] score 0-1) versus placebo, with no difference in mortality between the treatment groups. Compared with the 0-3 h window, there was no excess risk of symptomatic intracranial haemorrhage. We assessed the usefulness of additional endpoints and did subgroup and sensitivity analyses to further investigate the benefit of alteplase. ⋯ Boehringer Ingelheim.
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Dopamine is an essential neurotransmitter for many brain functions, and its dysfunction has been implicated in both neurological and psychiatric disorders. Parkinson's disease is an archetypal disorder of dopamine dysfunction characterised by motor, cognitive, behavioural, and autonomic symptoms. ⋯ We review clinical features, overlapping molecular mechanisms, and a specific cognitive mechanism of habit learning that might underlie these behaviours. We integrate these mechanisms with the emerging view of the basal ganglia as a distributive system involved in the selection and facilitation of movements, acts, and emotions.